A fermentation method that is a method of producing a substance involving culture of a microorganism or cultured cells can be roughly classified into (1) a batch fermentation method and a fed-batch or semi-batch fermentation method, and (2) a continuous fermentation method. The batch fermentation method and the fed-batch or semi-batch fermentation method have such advantages that facilities are simple, culturing is completed in a short time, and the possibility of being contaminated with germs other than cultured bacteria in fermentation of a product by pure culture of bacteria is low. However, the concentration of a product in a culture solution increases with time, and the productivity and yield decrease due to influences such as inhibition by the product and an increase in the osmotic pressure. Therefore, it is difficult to stably maintain high yield and high productivity for a long time.
In contrast, in the continuous fermentation method, high yield and high productivity can be maintained over a longer period by preventing accumulation of a target substance in a fermentor compared to the batch fermentation method and the fed-batch or semi-batch fermentation method. Conventional continuous culturing is a culturing method in which a fresh culture medium is supplied to a fermentor at a constant rate, a culture solution in the same amount as the amount of the culture medium is discharged out of the fermentor to always keep the amount of liquid in the fermentor constant. In batch culture, culturing is completed when the initial substrate concentration is consumed, and in continuous culturing, culturing can be theoretically continued infinitely.
Recently, a continuous culture apparatus using an organic macromolecular separation membrane has been proposed for continuous culture (for example, see International Publication No. 07/097260 and Japanese Laid-open Patent Publication No. 2008-212138).
However, the filtration ability of the separation membrane decreases by an SS (suspended solid) and an adsorbate attached to a filtration face, and a necessary amount of filtrate may not be obtained.
On the other hand, in the field of water treatment, not continuous fermentation, but scrubbing by supply of a gas has been proposed to wash a separation membrane (for example, see Japanese Patent No. 3645814).
However, in the continuous fermentation, the amount of oxygen in a fermentation liquid affects a result of fermentation. Therefore, simple application of a scrubbing method in the water treatment may cause a problem in which a chemical is not obtained at a desired rate.
In such a conventional technique, a scrubbing washing method suitable for continuous fermentation operation using a membrane separation technique has not been studied, and a method of maintaining the filtration properties of a separation membrane by washing a membrane surface and enhancing the productivity of a chemical by fermentation has been required.
It would therefore be helpful to provide a method of producing a chemical by a continuous fermentation method in which a washing effect of a separation membrane by a gas is enhanced by a simple operation procedure while high productivity can be stably maintained for a long time.